There have been numerous attempts in the prior art to develop lipid-based vesicles which are capable of entrapping various materials of interest ("passenger molecules"). The known methods have generally resulted in generally spherical vesicles known as liposomes which are composed of a lipid bilayer having an inner space in which the entrapped material is held. These vesicles have been formed by methods employing mechanical agitation, for example, sonication or extrusion. After lipids in organic solvents were mixed, the resulting mixture was dried, followed by mechanical agitation and rehydration with the passenger molecule to be entrapped to encourage the lipid bilayer to enclose around the passenger molecule.
The liposomes formed by this method were generally heterogeneous in size and difficult to sterilize for in vivo applications. The stability or shelf-life of these liposomes was often very limited. The entrapment efficiency of passenger molecules was generally limited. The methods required, in general, toxic nonbiocompatible solvents. The prior procedures were not applicable to aerosolization or formation of liposomes in situ. The vehicles formed by this method generally could be sterilized only by filtration as they exhibited heat lability. Moreover, prior methodology was not acceptably adaptable to the entrapment of certain passenger molecules.